Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6

Authors

  • Ryo Ueda,

    1. Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
    2. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
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  • Eiko Kinoshita,

    1. Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
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  • Rena Ito,

    1. Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
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  • Takeshi Kawase,

    1. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
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  • Yutaka Kawakami,

    1. Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
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  • Masahiro Toda

    Corresponding author
    1. Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
    2. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
    • Neuro-immunology Group and Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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    • Fax: +81-3-5363-3862


Abstract

We previously reported identifying SOX6 as a glioma antigen by serological screening using a testis cDNA library. Its preferential expression and frequent IgG responses in glioma patients indicate that SOX6 may be a useful target for immunotherapy. To examine whether cytotoxic T-lymphocyte (CTL) responses specific for SOX6 to destroy glioma can be generated in vivo, we treated glioma-bearing mice by vaccination with a plasmid DNA encoding murine full-length SOX6 protein. Following SOX6-DNA vaccination, CTLs specific for SOX6-expressing glioma cells were induced, while normal autologous-cells that had restrictedly expressed SOX6 during embryogenesis were not destroyed. Furthermore, DNA vaccination with SOX6 exerted protective and therapeutic antitumor responses in the glioma-bearing mice. This antitumor activity was abrogated by the depletion of CD4 positive T cells and/or CD8 positive T cells. These results suggest that the SOX6 protein has multiple CTL and helper epitopes to induce antitumor activity and the effectiveness of SOX6-DNA vaccine for the prevention and treatment of glioma. © 2008 Wiley-Liss, Inc.

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